The goal of this research is to understand the biology of solid tumor growth in terms of the mediators that tumors secrete that may trigger, block or otherwise interact with a variety of host defense systems including the clotting system, fibrinolysis, wound healing, and immunologic surveillance. The line 1 and 10 adenocarcinomas, syngeneic in strain 2 guinea pigs, will serve as a convenient model system; these tumors have distinctive growth patterns and very different biologic and immunologic properties. Initial studies will identify the various mediators that these tumors secrete, or that are associated with these tumor cells, including factors that l. alter vascular permeability; 2. activate the clotting system; 3. activate fibrinolysis; 4. inhibit macrophage migration; 5. inhibit monocyte chemotaxis; and 6. promote angiogenesis. In as far as possible, each of these mediators, but particularly the first three, will be purified. Other studies will concentrate on the mechanism by which these mediators affect tumor growth and host defenses. More specifically, antibodies will be prepared against the various mediators and fibrin and the effect of these on tumor growth will be assessed. The fibrin-gel that surrounds both tumors will be characterized and quantitated, and the effect of manipulation of this gel on tumor growth will be measured. Also to be examined is the effect of the fibrin-gel on both afferent and efferent limbs of the immune response. Finally, the physiology of the micro-vessels that tumors induce will be studied in terms of their permeability properties, their capacity to support inflammatory cell emigration, and the plasminogen activator associated with their endothelium.